CRG: This one goes up to 11: researchers crack code for genetic ‘control dials’

News from CRG

When a gene is switched on, various stretches of DNA nearby act as ‘control dials’, influencing the level of activity and the amount of gene product that is made. Using Mycoplasma pneumoniae bacteria as a model, CRG director Professor Luis Serrano and his team developed a rapid way of scanning through many thousands of randomly-generated DNA sequences in search of those that could efficiently activate a ‘reporter’ gene.

The researchers used the new technique, known as ELM-seq, to find DNA sequences that strongly increase the levels of transcription – the process by which a gene is ‘read’ to produce an intermediate message known as RNA. They also searched for sequences that enhance the efficiency of translation, when RNA messages are interpreted to build products such as protein molecules. The patented ELM-seq method relies on indirectly measuring the activity of a gene encoding a protein that adds a specific chemical ‘tag’ on to DNA. If the gene is more active it will leave more tags on the DNA. These tags are detected and measured using a sensitive DNA analysis technique known as massive, parallel sequencing, providing a quantitative readout of the gene’s activity levels.

Publishing their findings in the open-access journal Nature Communications, the researchers discovered DNA sequences for ‘control dials’ that consistently produce very high levels of gene activity. They also revealed previously unknown information about the kinds of DNA sequences that work best. Intriguingly, the team discovered that the very first ‘letter’ (base) of the RNA message is very important for efficient gene transcription.